The long term objectives of this proposal are to identify the antecedents of the obese condition and to develop successful strategies for prediction of, intervention in and successful reduced weight maintenance of individuals at risk for obesity. Our "LPL hypothesis" predicts that shifts in the "gating" function of adipose tissue LPL, whether genetically determined or environmentally induced, lead to altered lipid deposition, enlarged fat cell size, altered body composition, and permanently affect metabolic flux and partitioning. We plan to examine the effect of intervention measures on these factors. In addition, we propose to initiate studies to examine the effect of strain background on obesity associated pathology such as diabetes and increased susceptibility to dietary alterations. In addition we wish to explore the mechanisms whereby nutrient partitioning, substrate availability and LPL activity interact to affect lipid concentration in adipose tissue of normal and obese rats. In our proposed experiments we will examine the in vitro regulation of LPL metabolism directly at the cellular level using the adipoblast system derived from (obses) fafa and (lean) FaFa Zucker rats. We propose to examine LPL regulation and substrate partitioning in vivo using awake adult and young rats. in these in vivo studies, the role of blood flow, insulin and substrate availability will be related to adipose tissue LPL activity and triglyceride accumulation. Thus, the overall objectives of this proposal are directed toward an understanding of the development and pathogenesis of obesity, toward the development of more versatile animal models and toward an understanding of the regulation of adipose tissue lipoprotein lipase at both the cellular and organismal level.